A validated capillary electrophoretic method for the determination of indacaterol and its application to a pharmaceutical preparation

Indacaterol is a new inhaled ultra-long acting ${\beta }_2$-agonist. It has been recently approved in the European Union for the treatment of chronic obstructive pulmonary disease. This paper reports, for the first time, a method for the determination and validation of Indacaterol (IND) using an internal standard in capsules. Capillary electrophoretic separation was performed on an uncoated fused-silica capillary (50 cm effective length, 75 μm i.d.) and background electrolyte composed of 20 mmol L^?1 of sodium tetraborate buffer, 15% (v/v) methanol (pH = 10.0) with the application of 20 kV of potential; 10 s at 5 × 10³ N m^?2 (50 mbar) of injection time; and wavelength of 200 nm and 25 °C of temperature. The linearity was evaluated in the range of 4.90 × 10^?6 mol L^?1 (2.50 μg mL^?1) and 3.94 × 10^?5 mol L^?1 (20.00 μg mL^?1), with R = 0.9993 for inter-day. LOD and LOQ values were 2.18 × 10^?8 mol L^?1 (0.011 μg mL^?1) and 7.25 × 10^?8 mol L^?1 (0.037 μg mL^?1) for inter-day, respectively. The precision values were 0.50–1.06% for intra-day and 2.12% for inter-day as RSD%. The accuracy was tested by the standard addition method with the recovery values being between 98.79 and 99.09 as percentages with RSD% interval of 0.01–0.80. The developed method was validated according to ICH guidelines. Indacaterol was successfully determined in Arcapta^® capsule dosage form by the validated CE method with a relative error of 0.28%. The result was within the requirements of the USP 34-NF29. Therefore, the validated method may be used for the determination of Indacaterol in its capsules in quality control laboratories.     

Microbiological diagnostics of bloodstream infections in Europe—an ESGBIES survey

ObjectivesHigh-quality diagnosis of bloodstream infections (BSI) is important for successful patient management. As knowledge on current practices of microbiological BSI diagnostics is limited, this project aimed to assess its current state in European microbiological laboratories.MethodsWe performed an online questionnaire-based cross-sectional survey comprising 34 questions on practices of microbiological BSI diagnostics. The ESCMID Study Group for Bloodstream Infections, Endocarditis and Sepsis (ESGBIES) was the primary platform to engage national coordinators who recruited laboratories within their countries.ResultsResponses were received from 209 laboratories in 25 European countries. Although 32.5% (68/209) of laboratories only used the classical processing of positive blood cultures (BC), two-thirds applied rapid technologies. Of laboratories that provided data, 42.2% (78/185) were able to start incubating BC in automated BC incubators around-the-clock, and only 13% (25/192) had established a 24-h service to start immediate processing of positive BC. Only 4.7% (9/190) of laboratories validated and transmitted the results of identification and antimicrobial susceptibility testing (AST) of BC pathogens to clinicians 24 h/day. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from briefly incubated sub-cultures on solid media was the most commonly used approach to rapid pathogen identification from positive BC, and direct disc diffusion was the most common rapid AST method from positive BC.ConclusionsLaboratories have started to implement novel technologies for rapid identification and AST for positive BC. However, progress is severely compromised by limited operating hours such that current practice of BC diagnostics in Europe complies only partly with the requirements for optimal BSI management.     

Biomechanical comparison of a new technique of mandibular angle fractures: biplanar and bicortical superior proximal 3 holes and bicortical inferior plate fixation

Miniplates have been used for mandibular angle fractures during the past 2 decades. The technique of placing single miniplate at the upper border based on the tension lines of the fracture was proposed by Michelet and Champy. The need for a second miniplate to be applied to the lower mandible has been discussed recently. Biomechanical comparison of biplanar and monoplanar dual-miniplate fixation techniques was investigated by Haug. Our hypothesis is in dual-miniplate fixation; the proximal 3 holes of superior border miniplate could be fixated by bicortical screws. The first 2 are at the proximal bone segment and are not related to the tooth and also superior to the alveolar nerve. Generally, the third molar tooth is extracted because it is at the fracture site. Hence, the proximal third hole could also be fixated by bicortical screws. We define a biplanar dual-miniplate technique in which the lower plate and the proximal 3 holes of the upper plate are fixated by bicortical screws. We have designed a study for biomechanical comparison of our method and popular types of mandibular fixation methods.     

Acute kidney injury in hospitalized COVID-19 patients

International Urology and Nephrology - Acute kidney injury (AKI) in COVID-19 patients is associated with poor prognosis. However, the incidence, risk factors and potential outcomes of AKI in...     

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. Materials and method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.     

Can d-dimer become a new diagnostic parameter for acute appendicitis?

Introduction

In this study, we investigated d-dimer serum level as a diagnostic parameter for acute appendicitis.

Materials and Methods

Forty-nine patients were enrolled in the study. Patients were classified according to age; sex; duration between the beginning of pain and referral to a hospital or clinic; Alvarado scores; and in physical examination, presence of muscular defense, the number of leukocytes, preoperative ultrasonography, and d-dimer levels of histopathologic study groups were analyzed.

Results

Of the patients enrolled in the study, 26.5% were females and 73.5% males. The average age was 21 years (range, 16-38 years) and 81.7% acute appendicitis (AA). According the duration of pain, 63.2% of the patients were referred to the hospital within the first 24 hours, 26.5% of the patients were referred to the hospital within 24 to 48 hours, and 10.3% were referred to the hospital within a period of more than 48 hours. No statistically significant difference was determined regarding d-dimer levels between the histopathologic study groups (P > .05). Alvarado scores lower than 7 were found in 36.7% and 7 or higher in 63.3% of the patients. There was no statistically significant difference related with d-dimer levels between histopathologic study groups (P > .05). The ratio of cases with a number of leukocytes below the upper limit were determined respectively as 32.7% and 67.3%, and no statistically significant difference was found regarding d-dimer levels between histopathologic study groups (P > .05).

Conclusion

Increased d-dimer levels should not be considered as a diagnostic parameter in diagnosis of acute appendicitis.